As a basis for elucidating the mechanism of interaction of the glycopeptide antibiotic bleomycin with DNA a study is proposed to characterize bleomycin complexes with a series of nucleic acid derivatives: (1) mononucleotides (AMP, ADP, ATP, GMP and their corresponding deoxyribonucleotides), (2) self-complementary oligodeoxyribonucleotide duplexes (dG-dC and dA-dT types), with the appropriate degree of polymerization to be determined, and (3) double helical polydeoxyribonucleotides (poly dA-dT, poly dG-dC, poly dI-dC, and poly dA-dN, N equals 5 BrU and 5 IU). Preliminary experiments have demonstrated binding of bleomycin to representative members of each of the above classes of nucleic acid derivatives. The studies of a number of bleomycin derivatives--bleomycin-B2, phleomycin-D1, and tallysomycin-A and -B--will be conducted to delineate the structure-function relationship of these antibiotics. The present study will focus on binding of bleomycin to nucleic acid derivatives. Degradation of nucleic acids under the experimental conditions to be employed in these studies is minimal. The role of bleomycin and possible metal cofactors in nucleic acid degradation is deferred to a subsequent investigation which will be based largely on the results obtained in this study. This investigation will be conducted in close collaboration with Dr. Dinshaw J. Patel (Bell Telephone Laboratories). Nuclear magnetic resonance (NMR) (1H, 13C and 31P) spectroscopy will be the principal method to be employed. Assignments of appropriate spectral resonances to specific nuclei of bleomycin-A2, bleomycin-B2 and nucleic acid substrates are available. Fluorescence studies of bleomycin binding to nucleic acids and ultraviolet spectroscopic measurements of the effect of bleomycin on the thermal denaturation of nucleic acid duplexes will also be conducted.